Efficacy and safety of degludec versus Glargine in Type 2 Diabetes

Steven P Marso, Darren K McGuire, Bernard Zinman, Neil R. Poulter, Scott S. Emerson, Thomas R. Pieber, Richard E. Pratley, Poul Martin Haahr, Martin Lange, Kirstine Brown-Frandsen, Alan Moses, Simon Skibsted, Kajsa Kvist, John B. Buse

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Abstract

BACKGROUND Degludec is an ultralong-Acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-To-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. METHODS We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-To-Target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-To-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-Adjusted secondary outcome. RESULTS Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups. CONCLUSIONS Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529.).

Original languageEnglish (US)
Pages (from-to)723-732
Number of pages10
JournalNew England Journal of Medicine
Volume377
Issue number8
DOIs
StatePublished - Aug 24 2017

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Type 2 Diabetes Mellitus
Safety
Hypoglycemia
Glycosylated Hemoglobin A
Insulin
Insulin Glargine
insulin degludec
Glucose
Random Allocation
Chronic Renal Insufficiency
Meals
Cause of Death
Fasting
Cardiovascular Diseases
Stroke
Odds Ratio
Myocardial Infarction
Confidence Intervals
Incidence

ASJC Scopus subject areas

  • Medicine(all)

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Efficacy and safety of degludec versus Glargine in Type 2 Diabetes. / Marso, Steven P; McGuire, Darren K; Zinman, Bernard; Poulter, Neil R.; Emerson, Scott S.; Pieber, Thomas R.; Pratley, Richard E.; Haahr, Poul Martin; Lange, Martin; Brown-Frandsen, Kirstine; Moses, Alan; Skibsted, Simon; Kvist, Kajsa; Buse, John B.

In: New England Journal of Medicine, Vol. 377, No. 8, 24.08.2017, p. 723-732.

Research output: Contribution to journalArticle

Marso, SP, McGuire, DK, Zinman, B, Poulter, NR, Emerson, SS, Pieber, TR, Pratley, RE, Haahr, PM, Lange, M, Brown-Frandsen, K, Moses, A, Skibsted, S, Kvist, K & Buse, JB 2017, 'Efficacy and safety of degludec versus Glargine in Type 2 Diabetes', New England Journal of Medicine, vol. 377, no. 8, pp. 723-732. https://doi.org/10.1056/NEJMoa1615692
Marso, Steven P ; McGuire, Darren K ; Zinman, Bernard ; Poulter, Neil R. ; Emerson, Scott S. ; Pieber, Thomas R. ; Pratley, Richard E. ; Haahr, Poul Martin ; Lange, Martin ; Brown-Frandsen, Kirstine ; Moses, Alan ; Skibsted, Simon ; Kvist, Kajsa ; Buse, John B. / Efficacy and safety of degludec versus Glargine in Type 2 Diabetes. In: New England Journal of Medicine. 2017 ; Vol. 377, No. 8. pp. 723-732.
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abstract = "BACKGROUND Degludec is an ultralong-Acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-To-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. METHODS We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-To-Target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-To-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-Adjusted secondary outcome. RESULTS Of the patients who underwent randomization, 6509 (85.2{\%}) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7{\%}; 83.9{\%} of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5{\%}) in the degludec group and in 356 (9.3{\%}) in the glargine group (hazard ratio, 0.91; 95{\%} confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2{\%} in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9{\%}) in the degludec group and in 252 (6.6{\%}) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups. CONCLUSIONS Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529.).",
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TY - JOUR

T1 - Efficacy and safety of degludec versus Glargine in Type 2 Diabetes

AU - Marso, Steven P

AU - McGuire, Darren K

AU - Zinman, Bernard

AU - Poulter, Neil R.

AU - Emerson, Scott S.

AU - Pieber, Thomas R.

AU - Pratley, Richard E.

AU - Haahr, Poul Martin

AU - Lange, Martin

AU - Brown-Frandsen, Kirstine

AU - Moses, Alan

AU - Skibsted, Simon

AU - Kvist, Kajsa

AU - Buse, John B.

PY - 2017/8/24

Y1 - 2017/8/24

N2 - BACKGROUND Degludec is an ultralong-Acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-To-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. METHODS We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-To-Target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-To-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-Adjusted secondary outcome. RESULTS Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups. CONCLUSIONS Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529.).

AB - BACKGROUND Degludec is an ultralong-Acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-To-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. METHODS We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-To-Target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-To-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-Adjusted secondary outcome. RESULTS Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups. CONCLUSIONS Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529.).

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